Association of adipokines and inflammatory markers with lipid control in type 2 diabetes.

INTRODUCTION: Data regarding the effect of certain adipokines on lipid metabolism are equivocal. OBJECTIVES: The aim of this study was to evaluate the association of lipid control with adipokines and inflammatory markers in patients with type 2 diabetes. PATIENTS AND METHODS: The analysis included 195 patients with type 2 diabetes. The achievement of treatment targets in terms of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides was assessed in accordance with the current guidelines. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index as well as concentrations of highmolecular-weight (HMW) adiponectin, leptin, resistin, high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor α (TNF-α) were measured in all patients. Logistic regression analyses were performed to determine the risk factors for inadequate lipid control. RESULTS: Optimal control in terms of total cholesterol, LDL, HDL, and triglycerides was achieved in 61%, 43%, 53%, and 68% of the patients, respectively. In multivariate analyses, female sex, lower resistin concentrations, and the absence of statin treatment were predictors of total cholesterol levels above the treatment target; older age and lower statin dose--of LDL cholesterol levels above the treatment targets; female sex, higher HOMA-IR index, lower HMW adiponectin concentrations, and higher TNF-α concentration-o-f HDL levels below the treatment targets; and higher HOMA-IR, lower HMW adiponectin concentration, and the absence of statin treatment--of triglycerides above the treatment target. CONCLUSIONS: In type 2 diabetes, lower HMW adiponectin concentrations are associated with inadequate triglyceride and HDL control; higher TNF-α, with inadequate HDL control, and lower resistin concentrations, with inadequate total cholesterol control.

Effect of ASA dose doubling versus switching to clopidogrel on plasma inflammatory markers concentration in patients with type 2 diabetes and high platelet reactivity: the AVOCADO study.

BACKGROUND: The aim of the study was to compare the effects of 2 strategies of antiplatelet treatment (i.e., 150 mg ASA vs. 75 mg clpoidogrel) on plasma level of inflammatory markers in type 2 diabetes mellitus (T2DM) patients with high platelet reactivity (HPR). METHODS: Study cohort consisted of 304 T2DM patients on chronic ASA therapy (75 mg per day) participating in the Aspirin Versus/Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes (AVOCADO) study. Patients with HPR defined as Platelet Function Analyzer (PFA)-100 collagene/epinephrine closure time (CEPI-CT) < 193 s (n = 80) were randomized to 150 mg of ASA or 75 mg of clopidogrel in 2:3 ratio, respectively. Concentrations of the selected inflammatory markers, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, solubleCD40 ligand (sCD40L), and high sensitivity C-reactive protein (hsCRP), were measured and compared in both treatment groups before and after 8 weeks of treatment in both groups. RESULTS: Out of 234 patients included into final analysis, the total of 34.2% (n = 80) patients displayed HPR, of which 14.1% (n = 33) were randomized into 150 mg of ASA group and 20.1% (n = 47) into 75 mg of clopidogrel group. Treatment with clopidogrel was a positive predictor (stepwise multiple regression analysis) of reduction of sCD40L concentration (odds ratio [OR] 4.15; p = 0.013), while treatment with 150 mg ASA was a positive predictor of reduction of IL-6 concentration (OR 4.38; p = 0.033). There was no statistically significant differences between clopidogrel and ASA 150 mg treatment in respect to predictive value for decreased hsCRP concentrations or increased TNF-α concentrations. CONCLUSIONS: Increasing the dose of ASA from 75 mg to 150 mg daily or switching ASA 75 mg to clopidogrel 75 mg daily may reduce concentrations of some inflammatory markers (in particular hsCRP, IL-6 and CD40L) in T2DM patients with HPR treated previously with 75 mg of ASA.

Do statins influence platelet reactivity on acetylsalicylic acid therapy in patients with type 2 diabetes?

BACKGROUND: Type 2 diabetes (T2DM) patients are at increased risk of cardiovascular events despite long-term acetylsalicylic acid (ASA) therapy. This study was performed to establish the prevalence of high platelet reactivity (HPR) on ASA in T2DM and to identify its predictors. METHODS: The study included 185 T2DM on chronic ASA therapy and to assess platelet reactivity during long-term ASA therapy, we applied the point-of-care method VerifyNow(®) aspirin test (Accumetrics, San Diego, CA, USA). RESULTS: Compared with the low platelet reactivity (LPR) group, patients with HPR had higher triglyceride levels (145 vs. 118 mg/dL, p = 0.041), were less frequently treated with statins (57.1% vs. 75.3%; p = 0.038) and tumor necrosis factor-alpha (TNF-α) concentrations were higher (2.15 vs. 1.74 pg/mL; p = 0.052). In a multivariate analysis only statin therapy (OR 0.375; 95% CI 0.15-0.91; P = 0.030) and lower concentrations of TNF-α (for each 1.0 pg/ml: or 1.3; 95% ci 1.00-1.72; p = 0.046) were predictive of LPR. CONCLUSIONS: Our study provides indirect evidence that the beneficial effect of statins on platelet activity may be related to their non-lipid-mediated, pleiotropic mechanisms of action. This might have been partly related to decreased platelet reactivity in patients receiving statin therapy. In our study in patients with T2DM, platelet reactivity on ASA therapy measured with VerifyNow(®) was associated with TNF-α concentrations and statin therapy. These results may imply a role for subclinical systemic inflammation and a beneficial effect of statins in the development of HPR in T2DM.